Title:Network Pharmacology and Experimental Verification of Si Shen Decoction Regulating FABP4/PPARγ/NFκB Pathway in the Treatment of
Collagen-induced Arthritis
Volume: 28
Issue: 5
Author(s): Rui Guan, Jiashu Yao, Qing Qi, Jing Yu, Ruoshi Liu and Mingli Gao*
Affiliation:
- Rheumatology Department, The Affiliated
Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
Keywords:
Si Shen decoction, rheumatoid arthritis, FABP4, NFκB signaling pathway, network pharmacology, collageninduced arthritis.
Abstract:
Aim: This study aimed to investigate the mechanism of Si Shen Decoction (SSD) in
rats with Collagen-Induced Arthritis (CIA).
Background: Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral
symmetrical multi-joint pain and swelling. SSD has shown good results in treating RA in clinical
applications, but its mechanism of action remains unclear.
Objective: To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA).
Methods: Bioinformatics and network pharmacology analyses were used to predict the possible
treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase
chain reaction were used to verify the mechanism of SSD in the treatment of RA.
Results: FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD
treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD
group also significantly reduced the serum secretion of CRP, TNFα, and IL1β, decreased mRNA
levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot
showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and
phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the
FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The
therapeutic effect of SSD was significant with the increase of dose.
Conclusion: SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting
the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.
